The long-term objective of the PI's research program is to identify and understand the biochemical cause or causes of retinal photoreceptor cell dysfunction. Such information would be of profound medical significance and may provide insight into the biomedical changes which underlie loss of retinal function in diseases of the human retina. Analyses of retinas of animals possessing genetic mutations which compromise photoreceptor cell function and viability provide an expedient means for accomplishing this goal. The proposed studies will focus on identifying and understanding protein changes associated with photoreceptor dysfunction in retinas of rd (retinal degeneration) chicks. Studies of the rd chick retina provide a unique opportunity to investigate biochemical changes underlying photoreceptor cell dysfunction because total loss visual cell function in the retinas of these animals occurs in the absence of gross developmental abnormalities and precedes cellular degeneration. The primary biochemical site(s) for the rd mutation is not known. Preliminary two-dimensional gel electrophoretic analyses of proteins extracted from homozygous rd [rd/rd], heterozygous carrier [+/rd] and normal [+/+] retina during development and prior to the appearance of degeneration have revealed two groups of proteins whose expression is affected by the mutation. The proposed experiments will provide information concerning the biochemical identities of these proteins, their tissue-specificity and their cellular and subcellular locations within the tissues which produce them. Amino acid analyses, peptide maps and N- terminal or internal peptide amino acid sequences of these proteins will be used to determine the degree of homology between the proteins. Monospecific antisera raised against these proteins will be used to identify the cells which produce the proteins and their intracellular location. These data along with the amino acid sequence data will provide important clues regarding the cellular functions of these proteins. Together, these results will improve our understanding the biochemical changes underlying photoreceptor dysfunction in the rd chick retina and may provide insight into general biochemical processes which cause loss of photoreceptor function in retinal disease.